Introduction of formula feeding induces subclinical inflammation and altered chromatin structure in the intestine of preterm pigs

s of the 51st Workshop for Pediatric Research 51st Workshop for Pediatric Research Göttingen, Germany 16-17 April 2015 This supplement has not been sponsored. Meeting abstracts AimWhereas enteral nutrition has been recognized to play an important role for the development of necrotizingenterocolitis (NEC), the exact pathomechanism is still under debate [1, 2]. In this study we aimed to analyze howintroduction of enteral foods affects intestinal gene regulation and chromatin structure of different inflammatoryand pattern recognition genes (i.e. IL8, TLR2, TLR4, REG3A) in premature pigs before any clinical symptoms ofNEC.MethodsIn total 15 preterm piglets were either provided with total parenteral nutrition (n = 5) or minimal enteral nutrition -bovine colostrum (n = 5) or preterm infant formula (n = 5). Gene expression analyses of the genes mentionedabove were performed by quantitative PCR. Changes in chromatin conformation were assessed by endonucleasehypersensitivity assays. Functional studies analyzing the influence of chromatin conformation changes on theinflammatory response upon stimulation by lipopolysaccharide (LPS) were performed in CaCo-2 cells using thehistone deacetylase inhibitor Trichostatin A (TSA).ResultsEnteral feeding induced a significant up-regulation of pro inflammatory genes such as IL8 and TLR 4 in theabsence of any clinical symptoms of NEC. Those effects were more distinct in the formula fed subgroup comparedto piglets who received colostrum. Most up-regulated genes, particularly IL8 and TLR4, were associated withendonuclease hypersensitive regions and were thus located in de-condensed, active chromatin. In consistence withthis finding, TSA pretreated Caco-2 cells exhibit a significant higher IL 8 up-regulation after LPS exposurecompared to controls.ConclusionEnteral feeding in general and formula in particular influences the regulation of key inflammatory genes and theirrespective epigenetic signatures in the premature gut. This might contribute to the increased susceptibility to NECin premature infants. In consequence, more studies are urgently required to optimize enteral nutrition in preterminfants. References1. Morgan J, Young L, McGuire W: Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev 2013, 5: CD001970.2. Nanthakumar NN, Fusunyan RD, Sanderson I, Walker WA: Inflammation in the developing humanintestine: A possible pathophysiologic contribution to necrotizing enterocolitis. Proc Natl Acad Sci USA2000,97(11):6043–6048. 10.1073/pnas.97.11.6043